NM_001609.4:c.43-275A>G

Variant names:

• chr10-123034081-A-G
• rs4980245
• NM_001609.4:c.43-275A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001609.4(ACADSB):​c.43-275A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,284 control chromosomes in the GnomAD database, including 1,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1392 hom., cov: 33)
• Consequence: ACADSB NM_001609.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.651
• Publications: 0 publications found

Genes affected

ACADSB (HGNC:91): (acyl-CoA dehydrogenase short/branched chain) Short/branched chain acyl-CoA dehydrogenase(ACADSB) is a member of the acyl-CoA dehydrogenase family of enzymes that catalyze the dehydrogenation of acyl-CoA derivatives in the metabolism of fatty acids or branch chained amino acids. Substrate specificity is the primary characteristic used to define members of this gene family. The ACADSB gene product has the greatest activity towards the short branched chain acyl-CoA derivative, (S)-2-methylbutyryl-CoA, but also reacts significantly with other 2-methyl branched chain substrates and with short straight chain acyl-CoAs. The cDNA encodes for a mitochondrial precursor protein which is cleaved upon mitochondrial import and predicted to yield a mature peptide of approximately 43.7-KDa. [provided by RefSeq, Jul 2008]

ACADSB Gene-Disease associations (from GenCC):

• 2-methylbutyryl-CoA dehydrogenase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-123034081-A-G is Benign according to our data. Variant chr10-123034081-A-G is described in ClinVar as Benign. ClinVar VariationId is 1180240.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001609.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADSB	NM_001609.4	MANE Select	c.43-275A>G		intron	N/A	NP_001600.1	P45954-1
	ACADSB	NM_001330174.3		c.-163-275A>G		intron	N/A	NP_001317103.1	P45954-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACADSB	ENST00000358776.7	TSL:1 MANE Select	c.43-275A>G		intron	N/A	ENSP00000357873.3	P45954-1
	ACADSB	ENST00000908753.1		c.43-275A>G		intron	N/A	ENSP00000578812.1
	ACADSB	ENST00000908750.1		c.43-275A>G		intron	N/A	ENSP00000578809.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19646 AN: 152166 Hom.: 1393 Cov.: 33

Gnomad AFR AF: 0.0975

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0133

Gnomad SAS AF: 0.0583

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.165

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19647 AN: 152284 Hom.: 1392 Cov.: 33 AF XY: 0.126 AC XY: 9353 AN XY: 74470

African (AFR) AF: 0.0973 AC: 4044 AN: 41562

American (AMR) AF: 0.132 AC: 2016 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.216 AC: 750 AN: 3470

East Asian (EAS) AF: 0.0133 AC: 69 AN: 5186

South Asian (SAS) AF: 0.0584 AC: 282 AN: 4832

European-Finnish (FIN) AF: 0.0761 AC: 807 AN: 10608

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.165 AC: 11196 AN: 67996

Other (OTH) AF: 0.150 AC: 318 AN: 2114

Alfa AF: 0.159 Hom.: 2878

Bravo AF: 0.134

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.0
DANN	Benign	0.75
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4980245; hg19: chr10-124793597;